Review ArticleMethylprednisolone treatment in acute spinal cord injury: the myth challenged through a structured analysis of published literature
Introduction
Spinal cord injury (SCI) is a catastrophic event that imposes an enormous medical, psychological, social, and economic impact on individuals, families and society [1]. During the First World War, the immediate mortality of SCI was 50-65% [2]. Today, life expectancy after SCI in the industrialized world is only slightly reduced [3], [4]. In one study, the mean life expectancy of spinal cord injured people compared with that of the whole population was estimated to approach 70% for individuals with complete tetraplegia, 84% for complete paraplegia, and 92% for patients with an incomplete lesion (spared motor functional capabilities) [4]. Because there is a lack of effective treatment for restoring neurological function below the level of the injury, positive symptoms (such as spasticity and hyperreflexia) that interfere with the remaining function, and increased long-term survival [5], the majority of SCI victims face many years of lost independence and continued medical expenses.
In most cases, traumatic SCI is characterized by severe contusion rather that transection of the spinal cord, even when there are massive bony injuries [6]. However, the primary lesion is gradually enlarged by delayed secondary damaging processes [7], [8], [9], leading to necrotic changes and cavity formation of the injured spinal cord tissue [9], [10], [11]. The exact pathogenesis of secondary spinal cord damage has not been fully elucidated, but there is considerable evidence that it occurs within minutes and continues for days or weeks, resulting in further neurological deterioration [12]. Furthermore, secondary spinal cord damage has the propensity to worsen during the first few hours after injury, and thus treatment during this “window” of time has the potential to prevent or reduce the resulting neurological deficit. Unfortunately, there is incomplete knowledge of the exact time course of many secondary mechanisms, and therefore the exact therapeutic window in which to treat many of these processes is unknown [13].
Section snippets
Treatment of spinal cord injury
Surgical intervention following spinal trauma aims at preventing further mechanical damage to the spinal cord through reestablishing the stability of the vertebral column. However, it has not been shown to prevent the posttraumatic neurological deterioration, which starts immediately after injury and can progress over the following months to years [14]. The results of recent clinical studies of neuroprotective pharmacotherapy have shown only modest improvement in neurological recovery and
The national acute spinal cord injury studies
The NASCIS were conducted under the leadership of Michael Bracken at the department of epidemiology and public health at Yale University. All of the three studies were multicenter, randomized, double-blinded clinical trials.
Other clinical studies of MP treatment in SCI
Others could not reproduce results obtained in the NASCIS II and III. Here we will review the most relevant clinical studies. Several other double-blind studies, comparing MP with placebo, were not published mostly because of the great publicity that MP received that made comparing it with placebo unethical.
In 1993, Galandiuk et al. [48] studied 32 patients with cervical or upper thoracic SCI managed in an urban trauma center from January 1987 to February 1993. Fourteen patients who received
Complications associated with MP treatment
Besides the narrow trauma-to-treatment time window of 8 hours [49], [50], [53], [54], [55], the use of MP is associated with increased risk for infections [22], [27], [50]. In the NASCIS II, although not statistically significant, patients who received MP had a 2.6-fold higher incidence of pneumonia, required longer periods of assisted ventilation and more ICU time [51]. The NASCIS III patients who received 48MP treatment had a twofold higher incidence of severe pneumonia, a fourfold higher
Discussion
The literature search was conducted using the National Library of Medicine's search service (PubMed). Key words used for the search were Methylprednisolone, Spinal cord injury, Spine trauma, Secondary injury, The National Acute Spinal Cord Injury Study, NASCIS. The search period was 1980–2005. Only articles published in peer group reviewed journals were included. For the clinical part, only clinical trials were included and a total of 15 publications were found to satisfy the review criteria.
Conclusion
Based on the background of the enormous criticism that the NASCIS II and III have attained in the last few years, there have been many neurosurgical departments that have stopped using MP as a standard routine in acute SCI [36], [60]. It is also important to note that MP is not recommended for use in acute SCI according to the Food and Drug Administration [35].
Acute SCI is a catastrophic event that has severe consequences. The devastating nature of this type of injury should not be a motive to
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